The primary goals of this research are i) to establish differences in brain processing in the context of nervous system damage or dysfunction, and ii) to determine the potential for learning-induced plasticity to ameliorate the negative consequences of such changes. Over the past year we have primarily focused on the impact of amputation, and on establishing the structural brain changes that accompany learning/training. 1) Loss of somatosensory input (Protocol 08-M-0052, NCT00623818) Following limb amputation, over 90% of people report phantom sensations in their missing limb, often painful sensations (Phantom Limb Pain, or PLP). One current theory suggests that PLP is a direct result of cortical reorganization, an example of maladaptive plasticity. Mirror therapy has been used as a treatment for PLP. During this therapy, patients move their intact limb while looking in a mirror, making it seem as if their missing limb is moving. We are currently investigating the neural consequences of amputation and the impact of mirror therapy on brain activity over time. We are continuing to recruit unilateral limb amputees and monitoring brain activity with fMRI over a period of four weeks while the amputees undergo mirror therapy. We are trying to establish whether the presence of PLP correlates with cortical reorganization in the somatosensory and motor cortex (similar to that observed in our participants with macular degeneration) and whether the mirror therapy works by reducing the extent of cortical reorganization. 2) Learning/training (Protocol 93-M-0170, NCT00001360) First, we are conducting a long-term longitudinal study of participants learning different tasks (e.g. motor sequences) to determine how structural properties of the brain change over time. Over a period of four weeks, participants are trained in two different tasks and we collect extensive functional and structural MRI data over the course of training. While previous studies have identified structural changes associated with learning, even over the course of a couple of hours, our initial findings have highlighted a potential confound that needs to be accounted for in such studies. Specifically, we have found that the structural measures obtained with MRI fluctuate according to the time of day with decreases in gray matter thickness and increases in ventricular volume that may reflect the impact of factors such as hydration level. Second, we are investigating the impact of feedback (positive, negative) on motor learning. Groups of participants are trained on different motor tasks and either provided with positive, negative or pseudo-feedback. Training occurs in the MRI scanner and we are investigating changes in functional connectivity from pre- to post-learning and also changes in activation over the course of the learning itself. Establishing the nature, degree and consequences of plasticity in the adult cortex provides important insights into the potential for rehabilitative brain therapies following injury or dysfunction in the nervous system.